ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.181C>G (p.Pro61Ala)

dbSNP: rs113612866
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233504 SCV000285490 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-09-11 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on VHL protein function. ClinVar contains an entry for this variant (Variation ID: 238103). This variant has not been reported in the literature in individuals affected with VHL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 61 of the VHL protein (p.Pro61Ala).
Ambry Genetics RCV000562742 SCV000664708 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-12 criteria provided, single submitter clinical testing The p.P61A variant (also known as c.181C>G), located in coding exon 1 of the VHL gene, results from a C to G substitution at nucleotide position 181. The proline at codon 61 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002487051 SCV002780905 uncertain significance Chuvash polycythemia; Pheochromocytoma; Von Hippel-Lindau syndrome; Nonpapillary renal cell carcinoma 2021-11-10 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998848 SCV004831009 uncertain significance Von Hippel-Lindau syndrome 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces proline with alanine at codon 61 of the VHL protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with VHL-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.